ObjectiveThis study aims to investigate the inhibitory effect of Wutoutang on pannus formation in adjuvant-induced arthritis （AIA） rats with wind-cold-dampness Bi syndrome and its potential mechanism. MethodA total of 40 male SD specific pathogen-free （SPF） rats were selected and divided into blank group， wind-cold-dampness Bi syndrome group ［Complete Freund's Adjuvant （CFA）， 200 μg］， Wutoutang group （15 g·kg^-1·d^-1）， and indometacin group （10 mg·kg^-1） according to random number table method. Except for the blank group， the other groups were given wind-cold-dampness stimulation before the CFA injection. After the rats were administered for 30 days， the basic conditions， onset time， arthritis index score， and foot swelling volume of AIA rats with wind-cold-dampness Bi syndrome were observed. Finally， peripheral arterial blood， ankle joint， and synovial tissue were taken. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum hypoxia-inducible factor-1α （HIF-1α）， vascular endothelial growth factor A （VEGFA） protein content， and rheumatism， including anti-O （ASO）， C-reactive protein （CRP）， and rheumatoid factor （RF）. Hematoxylin-eosin （HE） staining revealed the changes in joint histomorphology. Immunohistochemistry was used to detect the expression of HIF-1α and VEGFA， two important proteins in the ankle pathway. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to reveal mRNA levels of HIF-1α， VEGFA， angiopoietin-1 （Ang-1）， and angiopoietin-2 （Ang-2） in rat synovial tissue. ResultThe foot swelling volume and arthritis score of AIA rats with wind-cold-dampness Bi syndrome were substantially higher （P<0.01） compared with the blank group. Serum CRP， RF， and ASO levels were considerably elevated （P<0.01）. HE staining showed obvious hyperplasia of ankle synovium and synovial inflammation， angiogenesis and pannus formation， and aggravated bone destruction， indicating successful modeling. After the intervention of Wutoutang， the onset time was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. The inflammatory hyperplasia of synovial tissue， angiogenesis and pannus formation， and bone destruction were alleviated. The mRNA levels of HIF-1α， VEGFA， Ang-1， and Ang-2 in the synovial membrane were significantly decreased （P<0.05， P<0.01）. The expressions of HIF-1α and VEGFA in serum and ankle joints were decreased （P<0.01）. In the indomethacin group， the onset time of the disease was delayed （P<0.01）. Foot swelling volume and arthritis score were decreased （P<0.01）. Serum CRP， RF， and ASO levels were significantly decreased （P<0.01）. HIF-1α/VEGFA/Ang signaling pathway was activated， and pathological tissue injury was improved. ConclusionWutoutang can delay the onset time of AIA rats with wind-cold-dampness Bi syndrome， reduce foot swelling volume， arthritis score， rheumatic activity， and improve joint histopathology. It can inhibit pannus formation， and its mechanism may be related to down-regulating the expression of the HIF-1α/VEGFA/Ang pathway.

Objective·To analyze the diversity and composition of the maternal gut microbiota and vaginal microbiota in late pregnancy,neonatal meconium microbiota and vernix caseosa microbiota,and analyze the similarities,differences and correlations.Methods·This is a prospective study.Maternal stool samples and vaginal swabs in late-pregnancy,and neonatal meconium samples were collected from 11 mother-infant pairs at Xinhua Hospital,Shanghai Jiao Tong University School of Medicine from August to November 2018;the vernix caseosa from three sites(forehead,axilla,and inguinal crease)and meconium samples were collected from 14 healthy newborns at International Peace Maternity and Child Health Hospital,Shanghai Jiao Tong University School of Medicine in December 2018.All births were vaginal deliveries.The 16S rRNA gene V3?V4 region sequencing was used.The diversity,composition and similarities/differences of the maternal gut microbiota,the vaginal microbiota,and the neonatal meconium microbiota from the 11 mother-infant pairs,as well as the neonatal vernix caseosa microbiota and the meconium microbiota from the 14 newborns were analyzed.Results·The number of operational taxonomic units(OTUs),ACE index,Chao1 index,and Shannon index of maternal gut microbiota were all higher than those of vaginal microbiota;the ACE indices and the Chao1 indices of the vernix caseosa microbiota at three sites were all higher than those of meconium microbiota(P<0.01).The β diversity varied among the maternal gut microbiota,vaginal microbiota,and neonatal meconium microbiota(P<0.01).The β diversity of neonatal vernix caseosa microbiota from three sites(forehead,axilla,and inguinal crease)was similar,but different from meconium microbiota(P<0.01).At the phylum level,the dominant bacteria were Firmicutes(52.76%)and Bacteroidetes(41.67%)in the maternal gut microbiota,Firmicutes(74.36%)and Actinobacteria(21.25%)in the maternal vaginal microbiota,and Firmicutes(84.22%)and Proteobacteria(8.80%)in the neonatal vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Proteobacteria in the two batches of samples(81.11%and 88.72%,respectively).At the genus level,the dominant bacteria were Bacteroides(35.42%)and Faecalibacterium(10.12%)in the maternal gut microbiota,Lactobacillus(69.10%)and Bifidobacterium(11.30%)in the vaginal microbiota,and Lactobacillus(79.81%)and Pseudomonas(3.23%)in the vernix caseosa microbiota.The dominant bacterium in the neonatal meconium was Escherichia in the two batches of samples(55.21%and 31.18%,respectively).Conclusion·The α diversity of maternal gut microbiota is higher than that of vaginal microbiota and neonatal meconium microbiota,and it is higher in neonatal vernix caseosa than that in meconium microbiota.The Firmicutes is the predominant phylum in the maternal late-pregnancy gut microbiota,vaginal microbiota,and neonatal vernix microbiota.Lactobacillus is the predominant genus in both maternal vaginal and neonatal vernix caseosa microbiota.Proteobacteria in phylum and Escherichia in genus are predominant in meconium microbiota.The microbiota composition is similar in vernix caseosa at different body sites,but there are differences between the vernix caseosa microbiota and meconium microbiota.

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10^-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

Rheumatoid arthritis(RA)is a common systemic autoimmune disease.Chronic synovial inflammation,angiogene-sis,pannus formation,joint destruction of cartilage and bone are important pathological characteristics in RA.Semaphorins(Sema)is a kind of secreted and membrane-bound glycoprotein with nerve guiding effect.Recent studies have shown that Sema family members play an important role in the various pathological stages of RA.Therefore,this paper reviews and discusses the latest research progress on the involvement of Sema family members in different pathological links of RA,which can help to find new feasible targets for RA and provide new research ideas for the pathogenesis of RA.

Objective To investigate the long-term incidence of in-stent stenosis(ISS)in patients with intracranial aneurysms receiving pipeline embolization device(PED)who showed no ISS at short-to-medium term follow-up examination.Methods The clinical data of patients,who received PED treatment at the Department of Neurointervention,First Affiliated Hospital of Zhengzhou University of China between April 2015 and June 2022,were retrospectively collected.The patients with intracranial aneurysms,who showed no ISS at the initial follow-up with DS A and completed＞12 months long-term follow-up check after treatment at the same hospital,were screened out,and their relevant clinical data and imaging materials were collected.The incidence of ISS occurring in postoperative＞12 months long-term follow-up was calculated.The ISS was defined as a＞25％lumen loss of the parent artery when compared with its lumen size measured immediately after PED implantation.Results A total of 57 patients with 61 aneurysms were enrolled in this study,and a total of 68 PEDs were implanted.Forty-one(67.21％)aneurysms were treated by PED implantation only,and 20(32.79％)aneurysms by PED plus spring coils.The median initial follow-up time was 184.0 days(119.0,212.5).At postoperative＞12 months long-term follow-up visit,DSA was employed for 35(57.38％)aneurysms,CTA was adopted for 22(36.07％)aneurysms,and 3D-SPACE sequence MR scan was performed in 4(6.56％)aneurysms.The median follow-up time was 538.0 days(407.5,678.0),and the incidence of ISS was 0％.No ISS-related neurological symptoms occurred in all patients.Conclusion In treating intracranial aneurysms with PED,the postoperative incidence of ISS is low.No ISS is found during the short-term follow-up period,and long-term follow-up results tend to indicate that no ISS events have occurred.

Objective To explore the predictive value of CT image texture analysis for early enlargement of hypertensive intracerebral hemorrhage.Methods One hundred and eight patients with hypertensive intracerebral hemorrhage were divided into enlarged hematoma group (positive group)and non-enlarged hematoma group (negative group),according to whether the volume of hematoma on 24 h follow up CT scan was more than 30% or 6 mL of the baseline CT.Phillis Radiomics Tool V93 software was used to segment the hematoma on CT plain scan images of two groups,four features of first-order and three of gray-level co-occurrence matrix (GLCM),thirteen of gray-level size zone matricx (GLSZM)and eleven of gray-level run-length matricx (GLRLM)were obtained.The differences of thirty-one texture features between the two groups were compared.The ROC curves of the features with statistical differences were analyzed.The independent predictors of early enlargement of intracerebral hemorrhage were screened by Logistic multivariate regression model.Results Among the one hundred and eight patients,twenty-eight were positive group and eighty were negative group.Skewness and long run low gray-level emphasis (LRLGE)in positive group were significantly higher than those in negative group (P＜0.05).There was no significant difference in the remaining twenty-nine features between the two groups (P＞0.05).ROC curve analysis showed that the AUC of Skewness,LRLGE and their combined diagnosis were 0.634,0.814 and 0.828,respectively.The independent variables were screened by stepwise regression analysis.The LRLGE (OR＝1.238,95%CI＝1.009－1.51 9,P＜0.05)was selected as the regression model, suggesting that LRLGE was an independent predictor of the early enlargement of intracerebral hemorrhage.Conclusion Texture analysis of CT images is helpful to predict the early enlargement of hypertensive intracerebral hemorrhage,and LRLGE based on GLRLM algorithm can be used as an independent predictor.

Objective: To explore the clinical value of new rapid pathological diagnosis technology in biliary biopsy by endoscopic retrograde cholangiopancreatography (ERCP). Methods: 7 patients with biliary biopsy by ERCP were selected. In the biliary biopsyoperation, a new type of rapid pathological diagnostic technique is used to perform cytological initial diagnosis of the biopsy tissue. According to the results of rapid pathological diagnosis of biliary biopsy operation, we analyzed the clinical value of new rapid pathological diagnosis technology in the biliary biopsy operation. Results: The new rapid pathological diagnosis technology requires little space and no pollution. The diagnosis takes about 2 to 3 minutes and does not affect the normal biopsy operation. 7 patients with biliary biopsy by ERCP under the assistance of this technique, 5 patients (71.4%) confirmed the requirement of biopsy quality and quantity for the first biopsy with the assistance of this technology and 2 patients (28.6%) met the requirements for biopsy quality and quantity after biopsy again. Conclusions Because of the blindness of biliary biopsy by ERCP, the quality and quantity of biopsy tissue are often not guaranteed. The new rapid pathological diagnosis technology can provide real-time pathological diagnosis during biliary biopsy by ERCP and improve the quality and quantity of biliary biopsy tissue, and the cost of this technology is low, which is suitable for popularization and implementation in hospitals at all levels.

Objective Grey red-backed voles (Myodes rufocanus) are agile, fierce and hard to catch, thus, it is difficult to judge their gender by external appearance, especially for the juvenile voles. Therefore, it may cause difficulties to their allocation and later breeding in laboratories. The aim of this paper is to establish a rapid, simple and accurate method for gender identification of grey red-backed voles. Methods Fresh hair follicles were taken from 6 adult male voles, 3 adult females and 14 4-week-old juvenile voles, 5 male and 5 female 9-week-old Wistar rats, and 5 male and 3 female 6-week-old BALB/c mice. The genomic DNA was extracted using Chelex-100 resin and the zinc-finger Y/X gene (ZFY/ZFX) and the gene of sex-determining region of the Y (SRY) chromosome were amplified by PCR, and a double PCR amplification method was established. Results The ZFY/ZFX gene and SRY gene were simultaneously amplified from the male voles, while only the ZFY/ZFX gene was amplified from the females. The gender of all 23 voles, 10 Wistar rats and 8 BALB/c mice were correctly identified with this method, and the PCR results were consistent with the phenotypic and autopsy results. Conclusions Using fresh hair follicles as experimental materials for gender identification of grey redbacked voles can alleviate shock and damage to the animals. The established double PCR amplification method is accurate, simple, rapid, and deserves to be used for gender identification of grey red-backed voles.

Objective To establish a breeding method ofMyodes rufocanus in the laboratory,collect their growth and reproduction data,and provide a basis for carrying out the experimental animalization.Methods Wild Myodes rufocanus caught in the Moranbong woodland were brought back to the laboratory.They were bred artificially in a large hard wall rodent negative pressure isolator.Their growth and reproduction data were recorded for evaluating the results of breeding.Results The Myodes rufocanus were successfully bred in the laboratory.The pregnancy rate was 54.55%.The average pregnancy length was 20.4 days(8 to 22 days).During one breeding period,they gave birth 2.9 times on average.The maximum number of births was 7 times,far more than the number tested under field conditions.The average litter size was 4.3±1.22.The highest litter number of a single nest was 8.The weaning rate of pups was 94.8%.The growth and development of pups were good.Conclusions The breeding method for Myodes rufocanus is established.The growth and reproduction data are tested too.The results of our study laid a foundation for the experimental animalization of Myodes rufocanus.